Clinical Infectious Diseases

SUPPLEMENT ARTICLE

Influence of Population Demography and Immunization

History on the Impact of an Antenatal Pertussis Program
Patricia Therese Campbell,1,2 Jodie McVernon,1,2,3 Peter McIntyre,4 and Nicholas Geard1
1
Melbourne School of Population and Global Health, University of Melbourne, 2Infection and Immunity, Murdoch Childrens Research Institute, Royal Children’s Hospital, 3Peter Doherty Institute for
Infection and Immunity, University of Melbourne, Parkville, Victoria, and 4National Centre for Immunisation Research and Surveillance, Children’s Hospital at Westmead, New South Wales, Australia

Background. Antenatal pertussis vaccination is being considered as a means to reduce the burden of infant pertussis in low- and
middle-income countries (LMICs), but its likely impact in such settings is yet to be quantified.
Methods. An individual-based model was used to simulate the demographic structure and dynamics of a population with char-
acteristics similar to those of LMICs. Transmission of pertussis within this population was simulated to capture the incidence of in-
fection in (1) the absence of vaccination; (2) with a primary course only (three doses of diphtheria, tetanus, and pertussis vaccines
[DTP3] commencing in 1985, 1995, or 2005 at 20%, 50%, or 80% coverage); and (3) with the addition of an antenatal pertussis program.
Results. Modeled annual incidence averaged over the period 2015–2024 reduced with increasing DTP3 coverage, regardless of the
year childhood vaccination commenced. Over the same period, the proportion of infants born with passive protection did not change
substantially compared with the prevaccination situation, regardless of DTP3 coverage and start year. We found minimal impact of
antenatal vaccination on infection in all infants when mothers were eligible for a single antenatal dose. When mothers were eligible
for multiple antenatal doses, incidence in infants aged 0–2 months was reduced by around 30%. This result did not hold for the full 0- to
1-year age group, for whom antenatal vaccination did not reduce infection levels.
Conclusions. While antenatal vaccination could potentially reduce infant mortality in LMICs, broader gains at the population level
are likely to be achieved by focusing efforts on increasing DTP3 coverage.
Keywords. pertussis vaccine; disease transmission; antenatal vaccination; immunity; computer simulation.

There is limited information about the disease burden from
pertussis globally. The most recent estimate of deaths from per-
tussis, largely limited to administrative data, is 60 000 deaths in
children <5 years old, the great majority in low- and middle-in-
come countries (LMICs) [1]. Clinical cases of pertussis are
grossly underreported in LMICs, due to less developed surveil-
lance systems, reduced access to healthcare services, and limited
diagnostic testing [2]. Although estimated worldwide coverage
of the primary course of pertussis vaccine was around 86% in
2014 [3], coverage in many LMICs, or regions within them, is
much lower [2]. While worldwide pertussis vaccination cover-
age has substantially improved since the inception of the Ex-
panded Programme on Immunization (EPI) [3], later
adoption of vaccination in LMICs, with variable coverage due
to supply and delivery issues and political instability, is likely
to have led to heterogeneity in disease burden [4]. Antenatal
pertussis vaccination, which could possibly be delivered in
Correspondence: P. T. Campbell, Melbourne School of Population and Global Health, University
of Melbourne, Level 3, 207 Bouverie Street, Carlton, VIC, Australia 3010 (patricia.campbell@
unimelb.edu.au).
Clinical Infectious Diseases® 2016;63(S4):S213–20
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted
reuse, distribution, and reproduction in any medium, provided the original work is properly
cited. DOI: 10.1093/cid/ciw520
LMICs at higher coverage levels than infant doses, may offer
an alternative to reduce the burden of disease in settings with
intractably low EPI coverage and/or timeliness. While antenatal
vaccination has provided improved pertussis control in settings
with long-standing, high-coverage childhood vaccination pro-
grams [5, 6], the likely impact of antenatal vaccination in
LMICs has not yet been quantified.
We have previously studied pertussis resurgence and mater-
nal vaccination programs in settings with long-standing, high-
coverage childhood vaccination programs [7, 8]. In our study of
maternal pertussis vaccination, we used an individual-based
model of pertussis transmission, incorporating household struc-
ture and calibrated to Australian conditions, as representative of
high-income countries, to investigate the drivers of pertussis re-
surgence and we compared antenatal and postnatal pertussis vac-
cination strategies under a number of different delivery options
[8]. The model found that risk of early infant cases was increased
by declining maternal immunity, due to reduced opportunities
for natural boosting of immunity arising from high vaccination
coverage. These findings reflected the experience of countries
using postnatal and antenatal vaccination [5, 6, 8, 9], where the
passive direct protection provided to infants by antenatal vacci-
nation led to substantially greater reductions in severe early in-
fant pertussis than achieved by postnatal vaccination.
In this study, we have extended our previous work to settings
with less mature vaccination programs. We have simulated our

Modeling Antenatal Pertussis Vaccination • CID 2016:63 (Suppl 4) • S213

individual-based model of pertussis transmission to estimate the
impact of antenatal pertussis vaccination in settings characterized
by higher fertility rates and larger household sizes, on the back-
ground of lower historical vaccine coverage and differing assump-
tions about current levels of uptake, derived from the broad
diversity of scenarios observed in the field. Assumptions regard-
ing likely achievable antenatal coverage are derived from existing
experience of maternal tetanus programs [10]. This extension of
our existing model was designed to inform considerations around
implementation of antenatal vaccination programs in LMICs.
METHODS
Demographic Model
We model the demographic structure and dynamics of a popula-
tion using a previously developed individual-based model that
characterizes individuals by their age, sex, and the household to
which they belong [11, 12]. Using stochastic simulation, we
track the life events occurring to these individuals: birth, death,
couple formation and dissolution, and leaving home. The model
is parameterized to broadly represent the demographics of a low-
and/or middle-income country, with high fertility rates resulting
in a population characterized by a higher growth rate (2.5%),
younger average age, and larger average household size compared
with that of a more developed country. The population of a given
country will be uniquely shaped by its own demographic trajecto-
ry, and we have not attempted to model a specific country scenar-
io, but rather to investigate the influence of demographic trends
shared by multiple LMICs. Further detail is provided in the
Supplementary Materials.
Despite the importance of population mixing to the transmis-
sion of infectious diseases, only a small number of studies have
been published that attempt to measure age-related rates of contact
between individuals. Social contact surveys focused on European
settings found high levels of mixing between people of the same
age (age-assortative mixing) and between parents and children (in-
tergenerational mixing) [13, 14]. Recent studies undertaken in
Zambia and South Africa [15], Vietnam [16], and Kenya [17],
while differing in their methodologies and the reported number
of contacts, showed that key patterns of age-assortative and inter-
generational mixing remain similar across different settings. Our
model simulates patterns of contact behavior that reflect the age
and household structure of the population and the observed ten-
dency for contact to occur among individuals of similar ages.
Epidemiologic Model
Population Model of Infection and Immunity
We apply the same pertussis-specific transmission model (Figure 1)
to the population as used in previous work [8]. In addition to their
demographic characteristics, we also track the current state of in-
fection or immunity of each individual.
Individuals who are naively susceptible to pertussis (Figure 1,
susceptible naive), having never been infected or vaccinated,
S214 • CID 2016:63 (Suppl 4) • Campbell et al
become infected (infectious naive) with a probability deter-
mined by their risks of household and community acquisition.
These risks depend on an individual’s age-specific community
mixing patterns, and the presence of infected individuals in
their household and the wider community. Once recovered, in-
dividuals are fully protected against infection (full immunity).
Over time, an individual’s immunity wanes ( partial immuni-
ty). Individuals who are exposed to infection at this stage have
their immunity boosted at a rate equivalent to the force of in-
fection, and regain full protection against infection (full immu-
nity) without contributing to the force of infection. Individuals
whose immunity wanes fully without being reexposed and
boosted become susceptible once again (susceptible primed),
with a reduced susceptibility to infection compared to their
first infection. If reinfected (infectious primed), these individu-
als are presumed to be less infectious than those experiencing
their first infection. As priming is assumed to permanently
modify infection risk and characteristics [18], the model distin-
guishes between those naively susceptible, and those with im-
mune systems primed by pertussis infection or vaccination.
The model includes parameters to quantify duration and de-
gree of infectiousness; duration and degree of natural, vaccine,
and maternally acquired immunity; rates of community mixing
between age groups; and transmission coefficients for the house-
hold and community settings. Parameter values for each individ-
ual are selected from the distributions described in Table 1. The
duration of infectiousness for cases in naive and primed individ-
uals has a mean of 21 days, consistent with published values [19].
The contribution of infections in primed individuals to the force
of infection is yet to be convincingly resolved for pertussis [7, 20];
we assume infections arising in susceptible primed individuals
are half as infectious as those in naive individuals.
We assume recently exposed or vaccinated individuals have a
short duration of full immunity (full immunity; sampled from
an exponential distribution with mean 9 months) followed by a
much longer duration of partial immunity ( partial immunity)
[7]. We assume differences in the mean duration of partial im-
munity to infection following exposure and booster vaccination
of an order of magnitude (74 and 6 years, respectively), consis-
tent with the findings of previous modeling studies [7, 21]. We
assume a duration of protection following the full primary
course of vaccination of 4 years, slightly less than that of booster
doses. Based on our previous compartmental modelling, we as-
sume susceptible individuals primed by infection or vaccination
(susceptible primed) are 0.6 times as likely to be infected as
those naively susceptible [7].
Maternal and Infant Immunity
Infants born to mothers with full or partial immunity, acquired
from natural infection or vaccination, start their lives fully pro-
tected against infection (maternal protection) by antibodies ac-
quired from their mothers. Once these passive antibodies have
Figure 1. Pertussis transmission model. Infants born to immune mothers (full immunity or partial immunity) start their lives with maternal protection and are fully protected
against infection, before waning into the naive susceptible state. Naive individuals are infected at a rate λ(t), and are fully protected on recovery (full immunity), before waning
into a partially immune state from which their immunity can be boosted ( partial immunity). If not reexposed, individuals wane to a primed susceptible state (susceptible
[ primed]) in which their rate of infection, σλ(t), is reduced compared to naive susceptibles (σ = 0.6). If infected from this primed state, individuals are less infectious than
those experiencing their first infection (infectious [ primed]). Successfully vaccinated individuals acquire full immunity and thereafter follow the same-state transitions as those
with immunity acquired following exposure, although with a reduced mean duration of protection. Mean durations in infectious and immune states are shown, with details
provided in Table 1.

waned below a threshold level, infants become fully susceptible
to infection (susceptible naive). Although passive antibodies
against pertussis wane rapidly, with the starting level likely re-
lated to the time elapsed since a mother’s natural infection or
vaccination [22], in previous work our results were relatively in-
sensitive to durations of passive protection ranging from 6 to 24
weeks [8]. Thus, here we sampled the duration of maternally ac-
quired immunity from a distribution with a mean of 12 weeks.
Infants born to nonimmune mothers start their lives naively
susceptible to infection.
Application of Childhood Vaccination in the Model
Our previous pertussis modeling showed the importance of the
duration of natural immunity and historical vaccine coverage in
driving long-term pertussis trends [7]. We therefore expected
that, for each setting, the time since introduction of infant vacci-
nation and coverage achieved would influence the impact of an
antenatal pertussis program. While many LMICs adopted diph-
theria-tetanus-pertussis (DTP) vaccines as part of the EPI in the
late 1970s to mid-1980s (eg, The Gambia; Senegal) [4, 23, 24], up-
take in other countries has been slower (eg, Nigeria) [25]. The
percentage of 1-year-olds receiving the full primary course in
LMICs is heterogeneous, in 2011 ranging from very low levels
in some countries, for example, Chad (22%), through low levels
in Nigeria (47%) and Ethiopia (51%) to >80% in many countries
such as Kenya (88%) [26]. To provide for the wide range of vac-
cination experiences across LMICs, in this study we simulated 9
combinations of vaccination start year and coverage. We allowed
for infant vaccination to commence in 1985, 1995, or 2005 and
for each of these implementation dates, we increased infant cov-
erage linearly from 0% in the year of introduction to 20%, 50%, or
80% after 8 years, with coverage remaining constant thereafter.
While recognizing that real coverage rates are subject to variation
due to a number of factors, our selected combinations cover a
broad range of population immunity profiles.
We applied routine infant vaccination as a primary course at 2,
4, and 6 months, assuming that infants either receive all 3 prima-
ry doses on time, or none, hereafter referred to as three doses of
diphtheria, tetanus, and pertussis vaccines (DTP3). Infants suc-
cessfully vaccinated obtained full immunity, with primary vaccine
failures retaining their naive susceptible state. The probabilities of
successful vaccination after each dose were calculated such that
53%, 81%, and 85% of vaccine recipients were protected against
infection after 1, 2, and 3 doses, respectively, following our previ-
ous model [8] and described in the Supplementary Materials.
Childhood boosters were not applied in the model due to limited
availability and variable uptake in LMICs [2].
Simulation of Antenatal Vaccination Programs
Simulations of the model for each of the combinations of DTP3
start year and coverage were run until the end of model year
2014, providing 9 different initial conditions for which we in-
vestigated the impact of antenatal vaccination. For each of the
9 initial conditions, 5 different antenatal vaccination scenarios
were simulated (20 simulation runs for each initial condition/
scenario combination), commencing in model year 2015 and
continuing for 10 years:
1. Baseline (infant schedule at 2, 4, and 6 months; continue
previous coverage);
2. Baseline + antenatal vaccination (single-dose eligibility;
maternal coverage equivalent to DTP3);
3. Baseline + antenatal vaccination (multidose eligibility;
maternal coverage equivalent to DTP3);
4. Baseline + antenatal vaccination (single-dose eligibility;
maternal coverage greater than DTP3);

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Table 1. Parameter Distributions for the Epidemiologic Model

Parameter Distribution Type Mean/Fixed Value

Duration of infectiousness (naive and primed) Gamma 3 wk

Shape parameter = 3
Infectiousness in primed individuals relative to naive Fixed value 0.5
Duration of full immunity (full immunity states [natural and vaccine]) Exponential 9 mo
Duration of partial immunity (partial immunity [natural] state) Exponential 74 y
Duration of partial immunity following DTP3 vaccination (partial immunity [vaccine] state) Exponential 4y
Duration of partial immunity following antenatal vaccination (partial immunity [vaccine] state) Exponential 6y
Susceptibility in primed individuals relative to naive Fixed value 0.6
Duration of maternally acquired immunity Gamma 12 wk
Shape parameter = 3

5. Baseline + antenatal vaccination (multidose eligibility;
maternal coverage greater than DTP3);
In the “single-dose eligibility” scenarios, a mother is eligible to
receive a single dose after the introduction of the antenatal pro-
gram; in the “multidose eligibility” scenarios, for each birth
after the introduction of the antenatal program a mother is eligible
to receive a vaccination dose. For the “maternal coverage greater
than infant” scenarios, maternal coverage was set to 60%, 75%, or
90% for DTP3 coverage of 20%, 50%, and 80%, respectively.
For each of the 9 initial conditions, first we report infection in-
cidence over the period 2015–2024 in children aged 0–2 months
and 0–1 year under baseline conditions (scenario 1). Second, we
report infection incidence over the period 2015–2024 in these
same age groups under each of the antenatal vaccination strate-
gies (scenarios 2–5). We expect the incidence of infection to
closely reflect the disease burden in these age groups, as these
are first pertussis infections occurring at an early age and are
therefore highly likely to be symptomatic.
RESULTS
Effect of Childhood Vaccination Program
Prior to the implementation of DTP3, model-generated inci-
dence patterns for exemplar stochastic realizations of the model
showed epidemics every 3–4 years, incidence rates in naive indi-
viduals approximating the size of the birth cohort, and 95% of
individuals experiencing their first infection before the age of 10.
We compared, over a 10-year period, the impact of 9 alterna-
tive DTP3 coverage/start year combinations. The impact of our
baseline vaccination scenario (DTP3 at 2, 4, and 6 months) on
annual infection incidence in infants aged 0–2 months averaged
over the period 2015–2024 is shown in Supplementary Figure 1,
and for those aged 0–1 year in Supplementary Figure 2. Inci-
dence over this period reduced with increasing DTP3 coverage,
regardless of the year of introduction. For moderate and high
DTP3 coverage (50% and 80%, respectively), incidence was
lower when introduction occurred later. Year of DTP3 intro-
duction did not affect incidence under our baseline scenario
when coverage was low (20%).
In our model, the introduction of a childhood vaccination
program had little effect on the proportion of infants born
with antibody passively acquired from their mother as a result
of exposure to Bordetella pertussis. Across our 9 combinations
of vaccination start year and vaccination coverage, this propor-
tion varied minimally from 0.88 (interquartile range [IQR],
0.88–0.88) for 80% DTP3 coverage introduced in 1985 to 0.94
(IQR, 0.94–0.94) for 20% DTP3 coverage introduced in 2005
(Table 2). This maintenance of infant passive protection result-
ed from the continued high circulation of pertussis in older age
groups, providing opportunities for regular boosting of adult
immunity.
Impact of Antenatal Vaccination
For each of our DTP3 start year/coverage initial conditions, we
compared the impact over a 10-year period of antenatal vacci-
nation delivered for the “single-dose eligibility” and “multidose
eligibility” scenarios at equivalent or greater coverage relative to
DTP3 coverage. The incidence of infection in 2 age groups, 0–2
months and 0–1 year, was considered to assess the ability of an-
tenatal vaccination: (1) to protect infants too young to be vac-
cinated (0–2 months) through provision of passive protection;
and (2) to reduce the overall burden of infant disease (0–1 year)
through indirect protection of infants and other household
members due to the mother’s immunity.
For infants too young to be vaccinated (0–2 months), the
provision of a “single-dose eligibility” antenatal vaccination
program produced a minimal impact on infection incidence
Table 2. Proportion of Infants Born With Passive Protection Acquired
From Their Mothers, With DTP3 and No Antenatal Vaccination in Place
Start Year
DTP3 Coverage 1985 1995 2005
20% 0.93 (0.93–0.93) 0.93 (0.93–0.93) 0.94 (0.94–0.94)
50% 0.91 (0.91–0.91) 0.92 (0.91–0.92) 0.94 (0.94–0.94)
80% 0.88 (0.88–0.88) 0.90 (0.89–0.90) 0.91 (0.91–0.91)
Data are presented as median (interquartile range).
Abbreviation: DTP3, three doses of diphtheria, tetanus, and pertussis vaccines.

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Figure 2. Annual infection incidence in 0- to 2-month-olds averaged over 2015–2024 for single- and multidose antenatal vaccination eligibility and coverage equivalent to, or
greater than, that for three doses of diphtheria, tetanus, and pertussis vaccines (DTP3). Rows represent year of DTP3 introduction; columns represent DTP3 coverage.

compared to baseline for all DTP3 initial conditions, irrespec-
tive of whether antenatal vaccination was delivered at equivalent
or greater coverage relative to DTP3 (Figure 2). By contrast, a
“multidose eligibility” antenatal vaccination strategy reduced
incidence for these infants under all DTP3 initial conditions,
with larger decreases as DTP3 coverage (and thus antenatal cov-
erage also) increased, regardless of vaccination start year (Fig-
ure 2). When antenatal vaccination was applied at a greater
coverage than DTP3 vaccination, incidence was further reduced
for initial conditions with low or medium DTP3 coverage.
Similarly, across all infants aged <1 year, a “single-dose eligi-
bility” antenatal vaccination strategy had little effect on infection
incidence compared to baseline over all DTP3 initial conditions
(Figure 3). Over this time frame, even when mothers were eligible
for multiple antenatal doses, reductions in incidence compared to
baseline were slight (around 5%), even when antenatal coverage
was greater than DTP3 coverage.
While an antenatal strategy in which mothers were eligible to
receive only a single dose had little effect on the proportion of
infants born with passive immunity, eligibility for multiple an-
tenatal doses increased this proportion, compared with having
DTP3 only in place (Figure 4).
DISCUSSION
Using an individual-based model of pertussis transmission, we
found that antenatal vaccination can reduce infection among in-
fants aged 0–2 months in settings characterized by high popula-
tion growth rates and large household sizes. More pronounced

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Figure 3. Annual infection incidence in 0- to 1-year-olds averaged over 2015–2024 for single- and multidose antenatal vaccination eligibility; and coverage equivalent to, or
greater than, that for three doses of diphtheria, tetanus, and pertussis vaccines (DTP3). Rows represent year of DTP3 introduction; columns represent DTP3 coverage.

reductions could be achieved if mothers are eligible for multiple
antenatal doses. Introducing an antenatal vaccination program in
LMICs could thus potentially reduce infant mortality by prevent-
ing infection among the most vulnerable 0- to 2-month age
group. Despite this reduction of infection risk in the 0- to 2-
month age group, across the full first year of life antenatal vacci-
nation has virtually no impact on the incidence of infection, even
when administered at greater coverage than DTP3. For infants
aged 0–1 year, the direct protection provided by DTP3 acts
more strongly to reduce infection incidence than the short-
lived protection provided by maternal antibodies. We therefore
anticipate that in LMICs, broader gains at the population level
would be achieved by focusing efforts on increasing DTP3 cov-
erage than implementing an antenatal vaccination program,
particularly if severe morbidity (and associated mortality) ex-
tends beyond the first 2 months of life.
Pertussis circulation has remained high in many LMICs, due
to the recency of vaccine introduction and limited DTP3 cover-
age. In such settings, a high proportion of infants are likely to be
born with maternal protection derived from their mother’s own
prior infection or immunity-boosting exposure. Therefore, there
are relatively few infants who stand to benefit from the passive
protection provided by antenatal vaccination compared with set-
tings in which high vaccine coverage has been longstanding.
When we examined the impact of antenatal pertussis vaccination
in Australia, the predicted reduction in infection incidence was
much more pronounced, due to the substantially lower propor-
tion of infants born without passive protection [8]. As DTP3

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Figure 4. Proportion of infants born with maternal protection over the period 2015–2024 for single- and multidose antenatal vaccination eligibility (dotted line shows results
under three doses of diphtheria, tetanus, and pertussis vaccines (DTP3) only); and coverage equivalent to, or greater than, DTP3, where DTP3 vaccination was introduced in
1985. Note that the y-axis does not start at 0, in order to more clearly show the differences between strategies.

coverage increases in LMICs, with a consequent decrease in cir-
culation, we could begin to see cohorts of women, vaccinated as
newborns, who have never been infected. As these women be-
come mothers, their pertussis antibody levels might be insuffi-
cient to provide passive protection to their infants, as may have
occurred in high-coverage settings. Estimation of the degree to
which pertussis vaccination has interrupted transmission in
LMICs is complex, as we are only just beginning to see cohorts
of adults for whom their first experience of pertussis was vacci-
nation rather than infection.
To anticipate a reduction in the proportion of infants born
without maternal protection—a condition that favors antenatal
vaccination—it is important to monitor pertussis in LMICs for
signs of a reduction in circulation. Monitoring of seropreva-
lence at a population level, particularly among women of child-
bearing age, is one possible way of assessing epidemiologic
trends. Reduced antibody levels, suggestive of reduced circula-
tion, would logically lead to a decrease in the proportion of ne-
onates born with passive protection.
Our model considers a population representative of a high
fertility setting under a range of idealized historic DTP3 sched-
ules. There is a great deal of demographic and epidemiologic di-
versity across LMICs, and the conclusions of our work need to
be interpreted in this light. In previous work, we found that
changes in vaccination schedule and coverage are important
drivers of pertussis epidemiology [7]. For our model to better
reflect the pertussis experience of a particular country, more de-
tailed information on historical demographic and vaccination
coverage trends would need to be incorporated.
Limited population-wide surveillance data for pertussis in
LMICs makes validation of our model challenging. Other
than research studies undertaken in small, intensively studied
populations, such as Senegal [23], many published studies re-
port pertussis prevalence in hospitalized patients or patients
with persistent cough, unlikely to accurately estimate pertussis
prevalence in the whole population [27–29]. In Senegal, as EPI
coverage increased from 13% in 1986 to 82%–84% after 1990,
cases in infants aged <2 months decreased from around 200
per 1000 to around 56 per 1000 [23]. Although this is a some-
what larger reduction than the roughly 30% we observed in our
model upon introduction of DTP3 at 80%, it is pleasing to note
that model-generated incidence rates after the introduction of
DTP3 are of the same order of magnitude as this published
study [23].
As with every modeling study, there are some necessary lim-
itations to our work. First, we consider infection in infants <1
year of age, which we assume to be indicative of the disease bur-
den in this age group. We do not quantify the incidence of in-
fection in children aged >1 year, as increasing age and prior
immunity to pertussis are known to complicate the relationship
between pertussis infection and disease. While the disease burden
in older age groups may still be quite important in LMICs, we
prioritized younger age groups, as the very young are more vul-
nerable to serious consequences of pertussis infection and death.
Second, we have not conducted formal sensitivity analyses
around our infection and disease assumptions, as our prior
modeling work showed that the impact of antenatal vaccination
was generally robust to these assumptions [8]. As in our previ-
ous publication, we have modeled a vaccine with a duration of
protection substantially lower than the duration of protection
provided by natural infection. Were vaccine immunity to persist
over a longer timescale, the effectiveness of the “single-dose”
strategy may be increased. However, given the extended span
of childbearing years (85% of births are for mothers aged 15–
35 years) in high-fertility settings, this protection would need
to be robust over at least 2 decades. While we assume that pas-
sive protection derived from mothers whose immunity results
from natural infection and boosting of immunity through expo-
sure is equivalent to that following vaccination, some uncertain-
ty exists around this assumption [22].

Modeling Antenatal Pertussis Vaccination • CID 2016:63 (Suppl 4) • S219

 Finally, we have not included any childhood booster vaccina-
tions in our model due to the considerable heterogeneity of
availability and coverage in LMICs. It is important to consider
the possibility that antenatal vaccination may blunt an infant’s
response to the DTP3 schedule [30], which may have implica-
tions in countries that do not provide a booster in early life.
Our work demonstrates the importance of considering local
context and drivers of disease in implementation of vaccine
programs. Historical vaccination coverage and the longevity of
the vaccine program need to be taken into account when esti-
mating the likely impact of introducing antenatal booster vacci-
nations. The model supports further assessment of maternal
seroprotection as an indicator of likely program success.
Supplementary Data
Supplementary materials are available at http://cid.oxfordjournals.org.
Consisting of data provided by the author to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the author, so
questions or comments should be addressed to the author.
Notes
Acknowledgments. Computing facilities were provided by the National
eResearch Collaboration Tools and Resources (NeCTAR) Project and the
Victorian Life Sciences Computation Initiative.
Author contributions. P. T. C., J. M., and N. G. conceived and designed
the experiments. N. G. performed the experiments. P. T. C., J. M., P. M., and
N. G. analyzed the data. P. T. C., J. M., P. M., and N. G. wrote the manuscript.
Financial support. This work was supported by the Australian Research
Council (grant numbers DP110101758 to J. M., and DE130100660 to N. G.)
and the National Health and Medical Research Council (NHMRC) (grant
numbers 1078068 to N. G. and J. M., and CDF1061321 to J. M.).
Supplement sponsorship. This article appears as part of the supplement
“Infant Pertussis Disease Burden in the Context of Maternal Immunization
Strategies,” sponsored by the Bill & Melinda Gates Foundation.
Potential conflicts of interest. J. M. has received support from Novartis
Vaccines, GlaxoSmithKline, CSL, Sanofi, and Pfizer outside the submitted
work; reports membership of the Australian Technical Advisory Group
on Immunisation (ATAGI), including chair of ATAGI’s pertussis working
group; and has received travel funding from the Bill & Melinda Gates
Foundation. P. M. has received institutional funding from NHMRC, the
Bill & Melinda Gates Foundation, and the World Health Organization.
All other authors report no potential conflicts. All authors have submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts
that the editors consider relevant to the content of the manuscript have been
disclosed.
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